Oral-ATO for TP53-mutated Myeloid Malignancies

Launched by THE UNIVERSITY OF HONG KONG · Jan 10, 2025

Keywords

ClinConnect Summary

This clinical trial is studying the effectiveness of a medication called oral arsenic trioxide (Arsenol ®) combined with vitamin C and other low-intensity therapies for patients with certain types of blood cancers, specifically those that have a mutation in the TP53 gene. The focus is on patients who have either not been treated before or those whose previous treatments have not worked. The trial is designed for adults aged 18 and older who have been diagnosed with acute myeloid leukemia (AML), myelodysplastic neoplasm (MDS), or chronic myelomonocytic leukemia (CMML) according to specific medical guidelines.

To participate, individuals must be willing to sign a consent form and have a TP53 mutation confirmed. They should have an overall good health status (rated as 0-2 on a specific performance scale), and women and men of childbearing age must agree to use contraception during the study. Participants can expect to receive the study treatment and be closely monitored by the research team. It’s important to note that individuals with certain health conditions or who have recently undergone significant medical treatments may not be eligible for this trial.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Willing and able to provide informed consent
• • 2. Age ≥18 years
• • 3. Diagnosis of acute myeloid leukemia (AML), myelodysplastic neoplasm (MDS) or chronic myelonocytic leukaemia (CMML) by World Health Organization (WHO) 2022 criteria (1, 3)
• • 4. Presence of TP53 mutation
• • 5. Previously untreated patients for Cohort A (Treatment-naïve), or Patients failing 1 or more lines of prior treatment for Cohort B (Relapsed and Refractory)
• • 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• • 7. Women of childbearing potential and fertile men must agree to use an approved method of contraception from Screening until 30 days after the last dose of oral arsenic trioxide, ascorbic acid, venetoclax and azacitidine/decitabine/oral-decitabine-cedazuridine.
• Exclusion Criteria:
• • Inclusion Criteria
• • 1. Willing and able to provide informed consent
• • 2. Age ≥18 years
• • 3. Diagnosis of acute myeloid leukemia (AML), myelodysplastic neoplasm (MDS) or chronic myelonocytic leukaemia (CMML) by World Health Organization (WHO) 2022 criteria (1, 3)
• • 4. Presence of TP53 mutation
• • 5. Previously untreated patients for Cohort A (Treatment-naïve), or Patients failing 1 or more lines of prior treatment for Cohort B (Relapsed and Refractory)
• • 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• • 7. Women of childbearing potential and fertile men must agree to use an approved method of contraception from Screening until 30 days after the last dose of oral arsenic trioxide, ascorbic acid, venetoclax and azacitidine/decitabine/oral-decitabine-cedazuridine.
• • Exclusion Criteria
• • 1. Use of an investigational agent within 14 days of study treatment (or at least 7 half-lives of that agent, whichever is longer), prior to the first dose of oral arsenic trioxide
• • 2. Known hypersensitivity to arsenic trioxide, ascorbic acid, venetoclax or azacitidine/decitabine/oral-decitabine-cedazuridine or their excipients.
• • 3. Uncontrolled, active infection
• • 4. Major surgery within 4 weeks of starting the study drug, or not recovered from side effects of surgery
• • 5. Any other serious medical conditions that could compromise study participation, in the opinion of the investigator
• • 6. Known HIV infection or known, active hepatitis B or hepatitis C infection
• • 7. Concurrent second active and non-stable malignancy (patients with a concurrent second active but stable malignancy, i.e., non-melanoma skin cancers, are eligible)
• • 8. Known history of long QT syndrome (LQTS) or corrected QT interval by Fridericia formula (QTcF) ≥ 480 ms
• 9. Evidence at the time of Screening of significant renal or hepatic insufficiency (unless due to hemolysis) as defined by any of the following local laboratory parameters:
• • 1. Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation or eGFR; using CKD-EPI) \< 40 mL/min
• • 2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 x the local upper limit of normal
• • 10. Pregnant or lactating females, or females planning to become pregnant at any time during the study
• • 11. Unwilling or unable to comply with the study protocol